星点设计-效应面优化去甲斑蝥素壳聚糖肝动脉栓塞微球的制备

 目的 应用星点设计-效应面优化去甲斑蝥素壳聚糖肝动脉栓塞微球的制备工艺，以提高微球性质的可预测性，并对微球的部分特性进行表征以及对微球的体外释药行为进行考察。方法 以微球收率、载药量、包封率、平均粒径和跨距为指标，计算各指标的归一值，并利用几何均数得出总评归一值 (overall desirability， OD)，去甲斑蝥素和壳聚糖的重量百分比 (X1)、油水比例 (X2) 、壳聚糖浓度 (X3) 3个主要因素的各水平进行多元线性回归和二项式拟合，并进行模型预测分析及方法验证。结果 OD值的二项式拟合方程较好 (r2>0.92，P<0.05)，以最优处方制备的微球平均粒径为123 μm，载药量为10.09%。预测值与实测值偏差均较小。结论 星点设计-效应面能更好的优化微球的处方工艺，增加模型的实用性。

Optimization of Norcantharidin-Loaded Chitosan Microspheres Preparation with Central Composite Design and Response Surface Methodology for Hepatocellular Chemoembolization

OBJECTIVE To study the preparation technique and the release in vitro of norcantharidin-loaded chitosan microspheres (NCTD-CS-MS) for hepatocellular chemoembolization, and to optimize the characteristics using central composite design. METHODS The effects of three independent variables, such as weight percent of NCTD and chitosan， volume percent of organic phase and water phase and chitosan concentration in acetic acid solution, were investigated on five response variables. Response variables selected were yield， drug loading， entrapment efficiency， mean diameter and span dispersity. The data was transformed into desirability. Overall desirability (OD) was calculated from the geometric mean of the five desirabilities of each formulation. The second-order polynomial and linear equations were fitted，and resulting equation were used to produce three dimensional response surface graphs， by which optimized experimental conditions were selected. RESULTS OD were found to be dependent on three independent variables， according to optimized experimental conditions (r2>0.92，P<0.05). The RESULTS showed that an optimized formulation contained mean diameter of 123 μm and drug loading of 10.09%. The observed values agreed well with model predicted values. CONCLUSION The central composite design and response surface methodology were successfully used to optimize the preparation of NCTD-CS-MS.